2nd National Conference Human Retroviruses and Related Infections Washington, DC - January 29 - February 2, 1995

Natl Conf Hum Retrovir Relat Infect 1995 Jan 29-Feb 2;2: (abstract no. 32)

Huang M, Martin MA, Freed EO
NIH, Bethesda, MD 20892-0460

The p6 Gag protein is derived from the C terminus of the p55 Gag precursor. Conflicting results have been reported regarding the role of p6 in virus particle production.

In this study, we introduced a series of nonsense or amino acid substitution mutations throughout p6 in a full-length HIV-1 proviral clone. Truncation of p6 resulted in a 20-fold reduction in the release of virus particles compared to wild type. The C-terminal domain of p6 does not appear to be involved in this process, since neither premature termination nor single amino acid substitution mutations significantly reduces progeny particle release compared to the p6 deficient mutant. Single amino acid changes of residues 7 to 10 (PTAP) markedly reduced particle production to a level observed with the p6 deficient mutant. In contrast, other individual amino acid substitutions within the N-terminal domain of p6 had little effect. Mutations in PTAP also delayed the onset of a productive virus infection in the CEM T-cell line while other mutations had little effect on infectivity. Electron microscopy revealed that an unusually high number of tethered budding particles in cells transfected with the PTAP mutants. PTAP is therefore a critical domain involved in late stage of viral particle production.

A mutation was introduced into the protease gene of the PTAP mutants to study further the role of p6 in virus particle production. Interestingly, the PTAP mutations did not reduce virus particle production in the context of the protease-defective proviral clone. These results suggest that Gag precursor processing by the viral protease might be linked, mechanistically, to virus release defect observed with p6 mutants.

Keywords: Cell Line, Gene Products, gag, Genes, gag, HIV-1, Mutation, Protein Precursors, S100 Proteins, S100A12 protein, human, Virion, genetics, p55 gag precursor protein, Human immunodeficiency, virus 1

Download abstract

1995-01-29
32

Copyright © 1995 - The American Society for Microbiology. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the American Society for Microbiology.